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Bile acid metabolites in serum: intraindividual variation and associations with coronary heart disease, metabolic syndrome and diabetes mellitus.

ABSTRACT: Bile acids (BAs) regulate glucose and lipid metabolism. In longitudinal and case-control-studies, we investigated the diurnal variation of serum concentrations of the 15 major BAs as well as the biosynthetic precursor 7?-hydroxy-4-cholesten-3-one (C4) and their associations, respectively, with coronary artery disease (CAD), diabetes mellitus type 2 (T2DM), and non-diabetic metabolic syndrome (MetS). In hourly taken blood samples of four healthy probands, the intraindividual 24 h variation of C4, conjugated and unconjugated BAs ranged from 42% to 72%, from 23% to 91%, and from 49% to 90%, respectively. Conjugated BA concentrations mainly increased following food intake. Serum levels of C4 and unconjugated BAs changed with daytime with maxima varying interindividually between 20h00 and 1h00 and between 3h00 and 8h00, respectively. Comparisons of data from 75 CAD patients with 75 CAD-free controls revealed no statistically significant association of CAD with BAs or C4. Comparisons of data from 50 controls free of T2DM or MetS, 50 MetS patients, and 50 T2DM patients revealed significantly increased fasting serum levels of C4 in patients with MetS and T2DM. Multiple regression analysis revealed body mass index (BMI) and plasma levels of triglycerides (TG) as independent determinants of C4 levels. Upon multivariate and principle component analyses the association of C4 with T2DM and/or MetS was not independent of or superior to the canonical MetS components. In conclusion, despite large intra- and interindividual variation, serum levels of C4 are significantly increased in patients with MetS and T2DM but confounded with BMI and TG.

SUBMITTER: Steiner C

PROVIDER: S-EPMC3215718 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Bile acid metabolites in serum: intraindividual variation and associations with coronary heart disease, metabolic syndrome and diabetes mellitus.

Steiner Carine C Othman Alaa A Saely Christoph H CH Rein Philipp P Drexel Heinz H von Eckardstein Arnold A Rentsch Katharina M KM

PloS one 20111114 11

Bile acids (BAs) regulate glucose and lipid metabolism. In longitudinal and case-control-studies, we investigated the diurnal variation of serum concentrations of the 15 major BAs as well as the biosynthetic precursor 7α-hydroxy-4-cholesten-3-one (C4) and their associations, respectively, with coronary artery disease (CAD), diabetes mellitus type 2 (T2DM), and non-diabetic metabolic syndrome (MetS). In hourly taken blood samples of four healthy probands, the intraindividual 24 h variation of C4, ...[more]

PMID: 22110577

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Project description:The objective of this study is to identify essential aspects influencing radiation dose in computed tomography [CT] of the chest, abdomen and pelvis by intraindividual comparison of imaging parameters and patient related factors. All patients receiving at least two consecutive CT examinations for tumor staging or follow-up within a period of 22 months were included in this retrospective study. Different CT dose estimates (computed tomography dose index [CTDIvol], dose length product [DLP], size-specific dose estimate [SSDE]) were correlated with patient's body mass index [BMI], scan length and technical parameters (tube current, tube voltage, pitch, noise level, level of iterative reconstruction). Repeated-measures-analysis was initiated with focus on response variables (CTDIvol, DLP, SSDE) and possible factors (age, BMI, noise, scan length, peak kilovoltage [kVp], tube current, pitch, adaptive statistical iterative reconstruction [ASIR]). A univariate-linear-mixed-model with repeated-measures-analysis followed by Bonferroni adjustments was used to find associations between CT imaging parameters, BMI and dose estimates followed by a subsequent multivariate-mixed-model with repeated-measures-analysis with Bonferroni adjustments for significant parameters. A p-value <0.05 was considered statistically significant. We found all dose estimates in all imaging regions were substantially affected by tube current. The iterative reconstruction significantly influenced all dose estimates in the thoracoabdominopelvic scans as well as DLP and SSDE in chest-CT. Pitch factor affected all dose parameters in the thoracoabdominopelvic CT group. These results provide further evidence that tube current has a pivotal role and potential in radiation dose management. The use of iterative reconstruction algorithms can substantially decrease radiation dose especially in thoracoabdominopelvic and chest-CT-scans. Pitch factor should be kept at a level of ≥1.0 in order to reduce radiation dose.

Project description:Background and aimsDyslipidemia has been identified as a major risk factor for cardiovascular disease. We aimed to identify metabolites and metabolite modules showing novel association with lipids among Bogalusa Heart Study (BHS) participants using untargeted metabolomics.Methods and resultsUntargeted ultrahigh performance liquid chromatography-tandem mass spectroscopy was used to quantify serum metabolites of 1 243 BHS participants (816 whites and 427 African-Americans). The association of single metabolites with lipids was assessed using multiple linear regression models to adjust for covariables. Weighted correlation network analysis was utilized to identify modules of co-abundant metabolites and examine their covariable adjusted correlations with lipids. All analyses were conducted according to race and using Bonferroni-corrected α-thresholds to determine statistical significance. Thirteen metabolites with known biochemical identities showing novel association achieved Bonferroni-significance, p < 1.04 × 10-5, and showed consistent effect directions in both whites and African-Americans. Twelve were from lipid sub-pathways including fatty acid metabolism (arachidonoylcholine, dihomo-linolenoyl-choline, docosahexaenoylcholine, linoleoylcholine, oleoylcholine, palmitoylcholine, and stearoylcholine), monohydroxy fatty acids (2-hydroxybehenate, 2-hydroxypalmitate, and 2-hydroxystearate), and lysoplasmalogens [1-(1-enyl-oleoyl)-GPE (P-18:1) and 1-(1-enyl-stearoyl)-GPE (P-18:0)]. The gamma-glutamylglutamine, peptide from the gamma-glutamyl amino acid sub-pathway, were also identified. In addition, four metabolite modules achieved Bonferroni-significance, p < 1.39 × 10-3, in both whites and African-Americans. These four modules were largely comprised of metabolites from lipid sub-pathways, with one module comprised of metabolites which were not identified in the single metabolite analyses.ConclusionThe current study identified 13 metabolites and 4 metabolite modules showing novel association with lipids, providing new insights into the physiological mechanisms regulating lipid levels.

Dataset Information

Bile acid metabolites in serum: intraindividual variation and associations with coronary heart disease, metabolic syndrome and diabetes mellitus.

Publications

Bile acid metabolites in serum: intraindividual variation and associations with coronary heart disease, metabolic syndrome and diabetes mellitus.

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